Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex

Psychopharmacology (Berl). 2003 Jul;168(3):344-6. doi: 10.1007/s00213-003-1440-z. Epub 2003 Apr 9.


Rationale: The dorsolateral prefrontal cortex (DLPFC) participates in the pathophysiology of mania. In particular, left-sided structural and metabolic abnormalities have been described.

Objectives: Clinical symptoms may be due to hyperactivity of cortical glutamatergic neurons, resulting in increased excitatory neurotransmitter flux and thus enhanced Glx levels.

Methods: Glutamate/glutamine (Glx) levels were assessed by proton magnetic resonance spectroscopy ((1)H-MRS) in eight acute manic patients compared with age- and gender-matched controls.

Results: Manic patients had significantly elevated Glx levels ( t-test; t=-3.1, P=0.008) within the left DLPFC.

Conclusions: Our results indicate that the prefrontal cortical glutamatergic system is involved in the pathophysiology of acute mania. This may have implications for the treatment of mania.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Bipolar Disorder / metabolism*
  • Choline / metabolism
  • Creatine / metabolism
  • Female
  • Glutamic Acid / metabolism*
  • Glutamine / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Prefrontal Cortex / metabolism*
  • Receptors, Glutamate


  • Receptors, Glutamate
  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate
  • Creatine
  • Choline